Detailed program for the 18th Symposium on Purine and Pyrimidine Metabolism in Man The program can be modified Tuesday June 11th 2019 Welcome cocktail at Le Sherrington 18.00-22.00 204B avenue des Frères Lumière, 69008 Lyon Wednesday June 12th 2019 The Auditorium, IARC 8.00-8.30 Arrival of participants and registration 8.30-8.40 Opening Session 1 8.40-10.40 Enzymes in purine and pyrimidine metabolism 1 Chairs: Santiago Ramón-Maiques & Wolfgang Knecht Targeting purine nucleotide metabolizing enzymes to S1.1 8.40-9.05 Mark Rider achieve AMP-activated protein kinase activation for the treatment of type 2 diabetes The purine intermediate AICAR impairs the mitotic spindle S1.2 9.05-9.20 Jim Dompierre assembly checkpoint by affecting the de novo pyrimidine biosynthesis pathway Doreen Dobritzch- Crystal structure and pH-dependent allosteric regulation of S1.3 9.20-9.40 Lohkamp human β-ureidopropionase An unexpected link between ecto-5’-nuclotidase deficiency S1.4 9.40-9.55 To be confirmed and impaired cardiac vitamin B12 metabolism Juan Manuel Reconstitution of human dihydroorotate dehydrogenase for S1.5 9.55-10.10 Orozco Rodriguez neutron scattering studies Blanca Martinez- DCTPP1 preserves genomic integrity through the S1.6 10.10-10.25 Arribas modulation of dCTP and dTTP homeostasis Extracellular metabolism of NAD+ and NMN on the surface S1.7 10.25-20.40 To be confirmed of murine lung endothelial cells 10.40-11.00 Coffee break Session 2 11.00-13.00 Drug development and targeting purine and pyrimidine metabolism Chairs: Suzanne Peyrottes & Frits Peters Targeting SAMHD1 to enhance nucleoside-based cancer S2.1 11.00-11.15 Sean Rudd therapies Sustained effectiveness, safety and therapeutic drug monitoring of thioguanine in a cohort of 274 Inflammatory S2.2 11.15-11.30 Chris Mulder Bowel Disease patients, intolerant for conventional therapies Effects Of Antiretroviral Therapy With Tenofovir And Other Antiretroviral Drugs On The Inflammatory State And Bone S2.3 11.30-11.45 Aránzazu Medieiro Remodeling On newly diagnosed HIV-Patients At Basal And 3 and 12 Months after starting Treatment Inhibition of Membrane Bounded Ecto-5′-nucleotidase S2.4 11.45-12.00 Jamshed Iqbal (CD73): A Novel Target for Treatment of Cervical Cancer Design and synthesis of purine nucleot(s)ide analogues as S2.5 12.00-12.15 Christophe Mathé CD73 inhibitors Drug discovery and optimization targeting CD73 to restore S2.6 12.15-12.30 Laurent Chaloin anticancer immune response Tormod Karlsen Sonoporation and gemcitabine delivery in pancreatic cancer S2.7 12.30-12.45 Bjånes cell lines Targeting NUDT15 to Improve the Anticancer Efficacies of S2.8 12.45-13.00 Simin Zhang Nucleoside Analogue Antimetabolites 13.00-14.30 Lunch and Poster session 1 Session 3 14.30-16.00 Purines and pyrimidines in cancer 1 Mounira Amor-Guéret & Jörgen Bierau Mapping and targeting pyrimidine nucleotide biosynthesis S3.1 14.30-14.55 Caius Radu and utilization in KRAS driven pancreatic cancer Role of miR-17 family on human Concentrative Nucleoside S3.2 14.55-15.15 Clara Boces Pascual Transporter 1 (hCNT1) modulation during carcinogenesis cN-II in the metabolic and proliferative profile of human S3.3 15.15-15.30 Simone Allegrini lung tumor cell line NIC-H292 Dexamethasone may decrease the efficacy of gemcitabine- S3.4 15.30-15.45 Adrien Jaramillo cisplatin but not of cytarabine; role of deoxycytidine kinase The expression and activity of thymidine kinase 1 and S3.5 15.45.16.00 Liya Wang deoxycytidine kinase is modulated by hydrogen peroxide and nucleoside analogs 16.00-16.30 Coffee break Session 4 16.30-17.20 Purine and pyrimidine pools Chairs: Veronika Barešova & Claus Desler Madsen Cardiac mitochondrial nucleotide pool and its role in the S4.1 16.30-16.45 Alicja Bulinska post-ischemic adenosine production Nucleotide pools dictate the identity and frequency of S4.2 16.45-17.00 Anders Clausen ribonucleotide incorporation in mitochondrial DNA Barbara Kutryb- Clinical correlations of extracellular nucleotide metabolism S4.3 17.00-17.15 Zajac ecto-enzymes in patients with calcific aortic valve disease Anne Simmonds Memorial Lecture 17.15-18.15 Monika Löffler This lecture is sponsored by PUMPA 19.30 Departure for dinner 20.00-23.30 Symposium dinner on the rivers Rhône and Saône – Hermès boat Thursday June 13th 2019 The Auditorium, IARC Session 5 9.00-11.00 Enzymes in purine and pyrimidine metabolism 2 Chairs: Doreen Dobritzsch-Lohkamp & Laurent Chaloin Santiago Ramón- CAD, a multienzymatic protein at the head of de novo S5.1 9.00-9.25 Maiques pyrimidine biosynthesis Structural investigation of enzymes of Mycobacterium S5.2 9.25-9.40 Davide M Ferraris tuberculosis involved in the synthesis of purine and pyrimidine nucleotides Analysis of the purine metabolic effect of allopurinol and its S5.3 9.40-9.55 Sekine Mai derivative 2 SAMHD1 deficiency affects DNA replication fidelity and S5.4 9.55-10.10 Chiara Rampazzo telomere homeostasis in human fibroblasts Miriam Yagüe Deciphering the role of HD52, a mitochondrial nucleotidase S5.5 10.10-10.30 Capilla essential for pyrimidine homeostasis in Trypanosoma brucei Effect of xanthine oxidoreductase inhibitors on purine S5.6 10.30-10.45 Ken Okamoto metabolism in mouse brain under hypoxic environment Ecto-5’-nucleotidase (CD73) deficiency in mice leads to age Paulina S5.7 10.45-11.00 dependent impaired L-arginine metabolism and endothelial Mierzejewska dysfunction 11.00-11.35 Coffee break and Poster session 2 Session 6 11.35-13.00 Inborn errors of purine and pyrimidine metabolism 1 Chairs: Yolanda Cámara & Sylvain Latour Deficiency of perforin and hCNT1, a novel inborn error of S6.1 11.35-12.00 Aida Mata-Ventosa pyrimidine metabolism, associated with a rapidly developing lethal phenotype due to multi-organ failure Ribonucleotide Reductase Subunit RRM1 is Required for S6.2 12.00-12.20 Jonathan Shintaku Mitochondrial DNA Maintenance via Regulation of dNTP and rNTP Pools Characterization and complementation of cellular models of S6.3 12.20-12.40 Norbert Minet CTPS1 and CTPS2 deficiencies A homozygous hypomorphic mutation is responsible for S6.4 12.40-13.00 Emmanuel Martin CTPS1 immunodeficiency : immunological and molecular characterization from a cohort study 13.00-14.30 Lunch and Poster session 2 Session 7 14.30-16.00 Purines and pyrimidines in cancer 2 Chairs: Tormod Karlsen Bjånes & Takahiro Yamauchi Acquired resistance to Fluorocyclopentenylcytosine (RX- Btissame El S7.1 14.30-14.50 3117) in non-small lung cancer cells is related to a decrease Hassouni of active RX-3117 nucleotides Claus Desler The importance of nucleotide metabolism for successful S7.2 14.50-15.10 Madsen immunotherapy for cancer What roles for the 5’-nucleotidases cN-II and CD73 in the S7.3 15.10-15.25 Octavia Cadassou interplay between the cancer cell and its innate immune microenvironment? How the combination of 6-mercaptopurine with febuxostat S7.4 15.25-15.40 Mihoko Morita affects xanthine oxidase activity in vitro Novel ProTide NUC-3373: a potent inhibitor of thymidylate S7.5 15.40-16.00 Fiona McKissock synthase 17.00-18.30 Sightseeing in the old city of Lyon 19.30-21.00 PPS Board Meeting Friday June 14th 2019 The Auditorium, IARC Session 8 8.30-9.50 Inborn errors of purine and pyrimidine metabolism 2 Chairs: Sandra Pérez-Torras & André van Kuilenburg S8.1 8.30-8.45 Michio Hirano Deoxynucleoside Therapy for Mitochondrial DNA Depletion Cora Blázquez- Age-related metabolic changes limit efficacy of S8.2 8.45-9.00 Bermejo deoxynucleoside-based therapy in TK2-deficient mice Preparation of standards for LC-MS/MS detection of various S8.3 9.00-9.15 Olga Součková metabolites of the de novo purine synthesis and their 3 analysis in urine samples of healthy controls and patients with unspecific neurological symptoms AAV-mediated gene therapy shows efficacy on the S8.4 9.15-9.35 Ferran Vila-Julià biochemical and neurological phenotype of the nucleoside- enhanced mouse model of MNGIE Pathological purinosome assembly in cell model systems with de novo purine synthesis and salvage pathway S8.5 9.35-9.50 Veronika Barešová deficiencies can be repaired by complementation with wt- protein 9.50-11.00 PPS General assembly 11.00-11.30 Coffee break Session 9 11.30-13.00 Advances in gout and dysuricemia Chairs: Ivan Šebesta & Kimiyoshi Ichida S9.1 11.30-11.45 Werner Löffler Refractory Gout – Does IT Exist? Rosa Torres Toll-Like Receptor 4 (TLR4) polymorphism rs2149356 and S9.2 11.45-12.00 Jiménez risk of gout in a Spanish cohort Determination of total purine and purine base content of 82 S9.3 12.00-12.15 Kiyoko Kaneko foodstuffs to help nutritional therapy for gout and hyperuricemia Urate transporter ABCG2 is a physiological exporter of S9.4 12.15-12.30 Tappei Takada uremic toxin indoxyl sulfate and a crucial factor influencing CKD progression Multiple novel loci are associated with serum uric acid levels S9.5 12.30-12.45 Akiyoshi Nakayama in Japanese population: a genome-wide meta-analysis Introduction of “Clinical Practice Guideline for Renal S9.6 12.45-13.00 Akiyoshi Nakayama Hypouricemia” 13.00-14.30 Lunch and Poster session 3 Session 10 14.30-16.00 Purines and pyrimidines in cancer 3 Chairs: Maria Grazia Tozzi & Caius Radu Mounira Amor- Cytidine deaminase deficiency: from genetic instability to S10.1 14.30-14.55 Guéret cancer in the general population Evolution of dihydropyrimidine dehydrogenase (DPD) S10.2 14.55-15.15 Jörgen Bierau diagnostics in a single center in a time-period of eight years Resistance to differentiation affects pyrimidine analogs S10.3 15.15-15.30 Godefridus J Peters sensitivity